The objective of this proposed research is to investigate the role of the prostaglandin system in regulating myocardial blood flow in the awake pig. Specifically the effects of prostaglandin stimulation (arachidonic acid, PGI2) and inhibition (indomethacin) will be determined. In addition, the role of the prostaglandin system as related to coronary autoregulation will be assessed. A unique animal model will be employed permitting the quantification of the direct steady state effects of vasoactive agents, apart from systemic effects, on regional myocardial blood flow in a physiologic setting. Vasoactive agents will be administered through a non-occlusive microcannula in the left anterior descending coronary artery of the awake pig. Blood flow to myocardium whose vasculature receives the infusion will be compared to remote non-perfused myocardium by the radioactive microsphere technique. Identification of perfused myocardium will be accomplished by the injection of a separately labeled microsphere through the perfusion cannula. Five separate investigations have been designed to assess the effects of intracoronary administration of the following agents on myocardial blood flow: 1) arachidonic acid alone and following systemic indomethacin; 2) PGI2 alone and following systemic indomethacin; 3) indomethacin alone; 4) phenylephrine and angiotensin following systemic indomethacin; and 5) indomethacin at basal and rapid atrial paced heart rates.